A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma (CARTITUDE-6)

A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible

The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Daratumumab; Drug: Cilta-cel

Detailed Description

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function.

JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT).

Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.

• Study Type: Interventional
• Enrollment (Actual): 759
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Princess Alexandra Hospital
  • Camperdown, Australia
    • Royal Prince Alfred Hospital
  • Herston, Australia
    • Royal Brisbane and Womens Hospital
  • Melbourne, Australia
    • Austin Hospital
  • Melbourne, Australia
    • Peter Maccallum Cancer Centre
  • Melbourne, Australia
    • Alfred Health
  • Murdoch, Australia
    • Fiona Stanley Hospital
  • Waratah, Australia
    • Calvary Mater Newcastle Hospital
  • Westmead, Australia
    • Westmead Hospital
• Belgium
  • Anderlecht, Belgium
    • Jules Bordet Instituut
  • Antwerp, Belgium
    • UZA
  • Ghent, Belgium
    • UZ Gent
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Edmonton, Canada
    • Cross Cancer Institute
  • Hamilton, Canada
    • McMaster University
  • Montreal, Canada
    • Hôpital Maisonneuve-Rosemont
  • Montreal, Canada
    • McGill University Health Centre
  • Ottawa, Canada
    • Ottawa Hospital Research Institute
  • Québec, Canada
    • (CHU) Centre Hospitalier Universitaire de Quebec Laval
  • Toronto, Canada
    • Princess Margaret Cancer Centre
  • Vancouver, Canada
    • Vancouver General Hospital
• Czechia
  • Brno, Czechia
    • Fakultni Nemocnice Brno
  • Králová, Czechia
    • Fakultni nemocnice Hradec Kralove
  • Ostrava, Czechia
    • Fakutni nemocnice Ostrava
  • Pilsen, Czechia
    • Fakultni nemocnice Plzen
• France
  • Lille, France
    • CHRU de Lille - Hopital Claude Huriez
  • Lyon, France
    • Hospices civils de Lyon
  • Nantes, France
    • CHU De Nantes - Hématologie Clinique
  • Poitiers, France
    • CHU Poitiers - Pôle régional de Cancérologie
  • Saint-Louis, France
    • Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis
  • Toulouse, France
    • CHU de Toulouse
• Germany
  • Cologne, Germany
    • University Hospital of Cologne
  • Hamburg, Germany
    • Universitätsklinikum Hamburg - Eppendorf
  • Leipzig, Germany
    • University Hospital of Leipzig
  • Tübingen, Germany
    • Tübingen
  • Würzburg, Germany
    • University hospital of Würzburg
• Greece
  • Athens, Greece
    • Attikon University General Hospital of Attica
  • Thessaloniki, Greece
    • 'G. Papanikolaou' Hospital of Thessaloniki
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Ramat Gan, Israel
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Japan
  • Bunkyō City, Japan
    • Juntendo University Hospital
  • Fukuoka, Japan
    • Kyushu University Hospital - Hematology/Oncology
  • Hokkaido, Japan
    • Hokkaido University Hospital-Department of Hematology
  • Hyōgo, Japan
    • Hyogo College of Medicine
  • Kanazawa, Japan
    • Kanazawa University Hospital
  • Nagoya, Japan
    • Nagoya City University Hospital - Department of Hematology & Oncology
  • Okayama, Japan
    • Okayama University Hospital - Hematology/Oncology
  • Osaka, Japan
    • Osaka Metropolitan University Hospital
  • Shibuya City, Japan
    • Japanese Red Cross Medical Center - Hematology
  • Shinjuku-Ku, Japan
    • Keio University Hospital - Hematology
  • Tōhoku, Japan
    • Tohoku University Hospital - Hematology
• Netherlands
  • Amsterdam, Netherlands
    • VU Medisch Centrum
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Nijmegen, Netherlands
    • Radboud UMC
  • Rotterdam, Netherlands
    • Erasmus MC
  • Utrecht, Netherlands
    • UMC Utrecht
• Norway
  • Oslo, Norway
    • Oslo University Hospital Ullevål - Oncology
• Spain
  • Badalona, Spain
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Instituto Catalán de Oncología
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario 12 De Octubre
  • Pamplona, Spain
    • CLINICA UNIV. DE NAVARRA, Pamplona
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Santiago de Compostela, Spain
    • Hospital de Santiago de Compostela
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • Hospital Universitario la Fe, Valencia
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska Universitetssjukhuset
  • Linköping, Sweden
    • Landstinget i Ostergotland-Universitetssjukhuset i Linkoping
  • Lund, Sweden
    • Skånes University Hospital Lund
  • Uppsala, Sweden
    • Akademiska sjukhuset
• Switzerland
  • Basel, Switzerland
    • Universitaetsspital Basel - Zentrum fur Hamato-Onkologie
  • Bern, Switzerland
    • Universitaetsspital Bern, Inselspital
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois (CHUV)Département d'oncologie
  • Zurich, Switzerland
    • Universitaetsspital Zuerich -Universitaeren Herzzentrum Zuerich
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Medical Centre
  • Cardiff, United Kingdom
    • University Hospital of Wales
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • San Diego, California, United States, 92093
      • UC San Diego Health Moores Cancer Center
    • San Francisco, California, United States, 94117
      • University of California San Francisco (UCSF)
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffit Cancer center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • The Bronx, New York, United States, 10467
      • Montefiore M-E Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.

• Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:

  1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
  2. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
• ECOG performance status of grade 0 or 1
• Clinical laboratory values within prespecified range.

Exclusion Criteria:

• Prior treatment with CAR-T therapy directed at any target.
• Any prior BCMA target therapy.
• Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
• Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
• Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
• Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
• Stroke or seizure within 6 months of signing Informed Consent Form (ICF)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: DVRd + ASCT+DVRd (Standard Therapy); Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years	Drug: Bortezomib; Bortezomib will be administered SC.; Drug: Dexamethasone; Dexamethasone will be administered orally.; Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Daratumumab; Daratumumab will be administered SC.
Experimental: Arm B: DVRd followed by Ciltacabtagene Autoleucel; Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles. Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist of 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years	Drug: Bortezomib; Bortezomib will be administered SC.; Drug: Dexamethasone; Dexamethasone will be administered orally.; Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously.; Drug: Fludarabine; Fludarabine will be administered intravenously.; Drug: Daratumumab; Daratumumab will be administered SC.; Drug: Cilta-cel; Cilta-cel will be administered intravenously; Other Names: JNJ-68284528

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression free survival is defined as the time from the date of randomization to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first	up to 10 years ( or 300 PFS events)
Sustained MRD-negative CR	Sustained MRD-negative CR is defined as being MRD negative by bone marrow aspirate, as determined by NGS with a sensitivity of at least 10-5, and meeting the IMWG criteria for CR, and with MRD-negativity status confirmed at a minimum 12 months apart and without any examination showing MRD-positive status or PD in between.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response (OR)	OR is defined as participants who achieve a partial response (PR) or better according to the IMWG criteria.	up to 17 years
Complete Response (CR) or better status	CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria.	up to 17 years
Overall Minimal Residual Disease (MRD) -negative CR	achieving MRD-negative CR, as determined by NGS at any time after the date of randomization before initiation of subsequent antimyeloma therapy.	up to 17 years
Time to subsequent antimyeloma therapy	Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.	up to 17 years
Progression Free Survival on Next-line Therapy (PFS2)	the time from the date of randomization to the date of event, defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death due to any cause, whichever occurs first.	up to 17 years
Overall Survival (OS)	Overall survival is measured from the date of randomization to the date of the participant's death.	up to 17 years
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score	The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	up to 17 years
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score	The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact.	up to 17 years
Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Scor	The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	up to 17 years
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score	The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).	up to 17 years
Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.	up to 280 days

Collaborators and Investigators

• Sponsor: Stichting European Myeloma Network
• Collaborators: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): August 1, 2040

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cellular Therapy; BCMA CAR-T; Newly Diagnosed Multiple Myeloma; CAR-T Therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Carboxylic Acids; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; Dexamethasone; Cyclophosphamide; fludarabine; daratumumab
• Other Study ID Numbers: EMN28/68284528MMY3005; 2021-003284-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes